Model for effects of structural disruptions on ADAR editing. Oval-shaped ADAR enzymes are shown, with a triangular binding site for target adenosines (red). For the sake of illustration, each ADAR is assumed to interact with ∼40 bp of an ∼90 base-paired dsRNA (complementary gray and black strands). (A) Because ADARs are not sequence-specific, many binding sites exist, which theoretically equal: (dsRNA length in base pairs) − (binding site size in base pairs) + 1, or 90 − 40 + 1 = 51. (B) In the presence of excess ADAR there will be one most energetically favorable complex, in this hypothetical example, two ADAR proteins per dsRNA, which can only be accommodated in one way, thus limiting the adenosines that can be targeted. (C) Under conditions of limiting ADAR, a structural disruption (green lollipop) is recognized so that ADARs bind in a particular register, creating an editing hotspot, and again, limiting the adenosines that can be targeted.
